What is the recommended approach for screening antihistaminic (anti-histamine) drugs?

Screening Approach for Antihistaminic Drugs

Second-generation antihistamines should be prioritized over first-generation agents for most patients due to their superior safety profile, particularly regarding sedation and cognitive impairment. 1, 2

Patient-Specific Screening Considerations

Age-Related Factors

• Second-generation antihistamines (fexofenadine, loratadine, desloratadine) are strongly preferred for older adults due to less sedation and fewer anticholinergic effects 2
• First-generation antihistamines can cause cognitive decline, especially in elderly populations 1
• No currently licensed antihistamines are contraindicated in children 12 years and older, though dosing and age restrictions vary for younger children 1, 2

Renal Impairment

• Acrivastine should be avoided in moderate renal impairment (creatinine clearance 10-20 mL/min) 1, 2
• Cetirizine, levocetirizine, and hydroxyzine doses should be halved in moderate renal impairment 1
• Cetirizine, levocetirizine, and alimemazine should be avoided in severe renal impairment (creatinine clearance <10 mL/min) 1
• Loratadine and desloratadine should be used with caution in severe renal impairment 1

Hepatic Impairment

• Mizolastine is contraindicated in significant hepatic impairment 1
• Alimemazine should be avoided in hepatic impairment due to hepatotoxicity risk 1
• Chlorphenamine and hydroxyzine should be avoided in severe liver disease due to inappropriate sedating effects 1

Pregnancy Considerations

• Best to avoid all antihistamines in pregnancy, especially during first trimester 1
• Hydroxyzine is specifically contraindicated during early pregnancy 1
• Chlorphenamine is often chosen when antihistamine therapy is necessary due to its long safety record 1
• Loratadine and cetirizine are FDA Pregnancy Category B drugs 1

Efficacy and Safety Screening

First-Generation vs. Second-Generation

• First-generation H1R antihistamines (diphenhydramine, hydroxyzine, chlorpheniramine) cause significant sedation 1, 3
• Second-generation H1R antihistamines (fexofenadine, cetirizine, loratadine) are equally or more effective with less sedation 4, 3
• Later-generation nonsedating H1R antihistamines (fexofenadine, cetirizine) are often used at 2-4 times FDA-approved doses for better efficacy 1
• Fexofenadine may offer the best overall balance of effectiveness and safety for most patients 5
• Cetirizine is the most potent antihistamine available but may cause sedation in about 10% of patients 5

Specific Antihistamine Properties

• Cyproheptadine is a sedating H1 antihistamine with extended anticholinergic and antiserotonergic activities that might help gastrointestinal symptoms 1
• Ketotifen is a sedating H1R antagonist approved for allergic eye disease but can be compounded as tablets 1
• Doxepin has useful antihistaminic properties but has sedating and anticholinergic side effects 1, 2
• H1R and H2R antihistamines work better as prophylactic than acute treatment 1

Screening for Potential Adverse Reactions

• First-generation antihistamines have high sedation potential that can impair driving ability and lead to cognitive decline 1, 3
• Performance impairment can occur without subjective awareness of drowsiness 3
• First-generation antihistamines with anticholinergic effects can cause dry mouth, dry eyes, constipation, and urinary retention 4, 3
• Antihistamines with anti-histamine activity must be discontinued before skin testing (desloratadine has the longest elimination half-life at 27 hours) 1
• There is no evidence that prophylaxis with H1-, H2-receptor antagonists prevents or reduces the severity of anaphylaxis 1

Screening Algorithm for Antihistamine Selection

1. Initial Selection: Choose a second-generation antihistamine (fexofenadine, loratadine, cetirizine, desloratadine) as first-line therapy 1, 3
2. Patient Assessment: Screen for age, renal/hepatic function, pregnancy status, and risk of sedation 1, 2
3. Specific Considerations:
   • For patients with high risk of sedation (e.g., drivers, students): Fexofenadine preferred 3, 5
   • For severe symptoms requiring maximum efficacy: Cetirizine (can be dose-titrated up) 5
   • For nighttime use when sedation is beneficial: Consider first-generation antihistamines 2
   • For renal or hepatic impairment: Adjust selection based on specific contraindications 1
4. Monitoring: Watch for adverse effects including sedation, falls, confusion, dry mouth, constipation, and urinary retention 2, 4
5. Dose Adjustment: It has become common practice to increase the dose above manufacturer's licensed recommendation for patients who do not respond when potential benefits outweigh risks 1

Special Clinical Scenarios

• Addition of an H2 antihistamine may sometimes give better control of urticaria than an H1 antihistamine alone 1
• For patients with chronic urticaria, offer the choice of at least two nonsedating H1 antihistamines as responses and tolerance vary between individuals 1
• For mild perioperative allergic reactions, premedication with antihistamines may be beneficial 1